..Finally, the use of persistent PKC inhibitors that lasted for 24 h demonstrated that the neuronal systems in these animals did not adapt by increasing the activity of other protein kinase cascades to re-establish morphine tolerance...

Paradoxical enhancement of bupivacaine anesthesia in mice by drugs that open sodium channels

A B LohmannDepartment of Pharmacology and Toxicology, Virginia Commonwealth University School of Medicine, Richmond, Virginia 23298-0613, USAPediatr Res 49:50-5. 2001

..Surprisingly, p.o. buprenorphine was nearly as efficacious as the s.c. route of administration. These results indicate that buprenorphine substitution therapy may be effective in fentanyl-dependent human infants...

The role of several kinases in mice tolerant to delta 9-tetrahydrocannabinol

..In addition, inhibition of PKA reversed a decrease in dynorphin release shown to accompany THC tolerance in rats. These data support a role for PKA and Src tyrosine kinase in phosphorylation events in delta(9)-THC-tolerant mice...

How important is protein kinase C in mu-opioid receptor desensitization and morphine tolerance?

..Here, we propose that protein kinase C could have a crucial role in the desensitization of mu-opioid receptors by morphine and that this cellular process could contribute to the development and maintenance of morphine tolerance in vivo...

..Taken together, our results suggest the hypothesis that mGluRs are coupled to the NMDAR channels through the NR2B subunit in the spinal cord and that this coupling involves the activation of protein kinase C and protein kinase A...

Evidence for an important role of protein phosphatases in the mechanism of morphine tolerance

..These results are in agreement with our previous study in which we demonstrated that the same active mGluR5 antagonists blocked glutamate-mediated mobilization of internal calcium in a selective mGluR5 in vitro efficacy assay...

Pre-treatment with a PKC or PKA inhibitor prevents the development of morphine tolerance but not physical dependence in mice

..However, it appears that tolerance can be dissociated from physical dependence, indicating a role for PKC and PKA to affect antinociception but not those signs mediated through the complex physiological processes of withdrawal...

Determination of the role of conventional, novel and atypical PKC isoforms in the expression of morphine tolerance in mice

..Epinephrine augmented the enhancement by ibutilide of bupivacaine's potency by 6.8-fold. In summary, ibutilide may enhance the effects of bupivacaine by blocking K(+) channels on sensory nociceptive nerves...

..However, co-administration of bisinolylmaleimide I with KT-5720 or Gö-7874 with KT-5720 completely reversed the tolerance. This demonstrates that tolerance in a non-behavioral system involves the actions of PKC and PKA...

..2-fold at 2-h and 7.2-fold at 4-h when co-administered with THC. These results indicate that the enhancement of transdermal opioids by THC could lead to the design of an effective combination analgesic patch...

Synthesis and pharmacological evaluation of phenylethynyl[1,2,4]methyltriazines as analogues of 3-methyl-6-(phenylethynyl)pyridine